The neuroprotective effect of mycophenolic acid via anti-apoptosis in perinatal hypoxic-ischemic brain injury / 소아과
Korean Journal of Pediatrics
;
: 686-693, 2007.
Article
in English
| WPRIM
| ID: wpr-168239
ABSTRACT
PURPOSE:
Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a potent inhibitor of inosine-monophosphate dehydrogenase (IMPDH), a new immunosuppressive drug used. It was reported that MPA protected neurons after excitotoxic injury, induced apoptosis in microglial cells. However, the effects of MPA on hypoxic-ischemic (HI) brain injury has not been yet evaluated. Therefore, we examined whether MPA could be neuroprotective in perinatal HI brain injury using Rice-Vannucci model (in vivo) and in rat brain cortical cell culture induced by hypoxia (in vitro).METHODS:
Cortical cells were cultured using a 18-day-pregnant Sprague-Dawley (SD) rats and incubated in 1% O2 incubator for hypoxia. MPA (10 microgram/mL) before or after a HI insult was treated. Seven-day-old SD rat pups were subjected to left carotid occlusion followed by 2 hours of hypoxic exposure (8% O2). MPA (10 mg/kg) before or after a HI insult were administrated intraperitoneally. Apoptosis was measured using western blot and real-time PCR for Bcl-2, Bax, caspase-3.RESULTS:
H&E stain revealed increased brain volume in the MPA-treated group in vivo animal model of neonatal HI brain injury. Western blot and real-time PCR showed the expression of caspase-3 and Bax/Bcl-2 were decreased in the MPA-treated group In in vitro and in vivo model of perinatal HI brain injury,CONCLUSION:
These results may suggest that the administration of MPA before HI insult could significantly protect against perinatal HI brain injury via anti-apoptotic mechanisms, which offers the possibility of MPA application for the treatment of neonatal HI encephalopathy.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Oxidoreductases
/
Brain
/
Brain Injuries
/
Blotting, Western
/
Rats, Sprague-Dawley
/
Apoptosis
/
Neuroprotective Agents
/
Cell Culture Techniques
/
Models, Animal
/
Caspase 3
Limits:
Animals
Language:
English
Journal:
Korean Journal of Pediatrics
Year:
2007
Type:
Article
Similar
MEDLINE
...
LILACS
LIS